Publications by authors named "H Boutzen"

Article Synopsis
  • Scientists are studying leukemia stem cells (LSCs) because they help acute myeloid leukemia (AML) grow, and there's a lot of variety in them that was not fully understood before.
  • They used a special cell model from patients called OCI-AML22 to learn more about these different types of LSCs.
  • They found two main LSC subtypes that behave differently, which can help in creating better treatments for AML by targeting these specific types of cells.
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Unlabelled: Leukemia stem cells (LSC) possess distinct self-renewal and arrested differentiation properties that are responsible for disease emergence, therapy failure, and recurrence in acute myeloid leukemia (AML). Despite AML displaying extensive biological and clinical heterogeneity, LSC with high interleukin-3 receptor (IL3R) levels are a constant yet puzzling feature, as this receptor lacks tyrosine kinase activity. Here, we show that the heterodimeric IL3Rα/βc receptor assembles into hexamers and dodecamers through a unique interface in the 3D structure, where high IL3Rα/βc ratios bias hexamer formation.

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Many cancers are organized as cellular hierarchies sustained by cancer stem cells (CSC), whose eradication is crucial for achieving long-term remission. Difficulties to isolate and undertake in vitro and in vivo experimental studies of rare CSC under conditions that preserve their original properties currently constitute a bottleneck for identifying molecular mechanisms involving coding and non-coding genomic regions that govern stemness. We focussed on acute myeloid leukemia (AML) as a paradigm of the CSC model and developed a patient-derived system termed OCI-AML22 that recapitulates the cellular hierarchy driven by leukemia stem cells (LSC).

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Article Synopsis
  • * IDH mutations found in preleukemic stem cells are stable at relapse, suggesting that targeting these cells could help achieve long-term remission in AML patients with IDH mutations.
  • * Research indicates that the oncometabolite (R)-2-HG produced by IDH mutant enzymes activates vitamin D receptor pathways, enhancing the differentiation of AML cells when treated with ATRA and/or vitamin D, offering a new therapeutic strategy for these patients.
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Continuous supply of immune cells throughout life relies on the delicate balance in the hematopoietic stem cell (HSC) pool between long-term maintenance and meeting the demands of both normal blood production and unexpected stress conditions. Here we identified distinct subsets of human long-term (LT)-HSCs that responded differently to regeneration-mediated stress: an immune checkpoint ligand CD112 subset that exhibited a transient engraftment restraint (termed latency) before contributing to hematopoietic reconstitution and a primed CD112 subset that responded rapidly. This functional heterogeneity and CD112 expression are regulated by INKA1 through direct interaction with PAK4 and SIRT1, inducing epigenetic changes and defining an alternative state of LT-HSC quiescence that serves to preserve self-renewal and regenerative capacity upon regeneration-mediated stress.

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